Med Check

Industry Briefs

• On May 2, Targacept announced that AstraZeneca will not exercise its option to license Targacept's product candidate TC-5619, a highly selective alpha7 neuronal nicotinic receptor modulator. Targacept recently completed two phase 2 clinical trials of TC-5619, one in patients with schizophrenia and one in adults with attention-deficit/hyperactivity disorder (Psychiatric News, May 20). The company is currently conducting clinical and nonclinical studies to enable additional phase 2 development in Alzheimer's disease. Targacept retains full rights to the compound.

• On May 9, Heptares Therapeutics announced it has signed an exclusive option agreement with Shire Pharmaceuticals for a novel adenosine A2A antagonist discovered by Heptares and currently in preclinical development. Adenosine A2A is a G-protein coupled receptor involved in regulation of dopaminergic pathways in the brain. Recently, inhibition of the A2A receptor has been shown to be effective in treating symptoms of Parkinson's disease and may offer benefits in additional CNS disorders. Under the terms of the agreement, Heptares has granted Shire an exclusive option, upon completion of certain preclinical studies, to license worldwide development and commercial rights to the Heptares A2A program.

Legal Briefs

• On May 9, a lawsuit was filed in U.S. District Court in Pittsburgh by the families of Sean and Natalie Wain of Economy, Pa., on behalf of the couple's four children. The lawsuit was filed nearly two years after Sean Wain shot and killed his wife, Natalie, and then himself. The lawsuit alleges that Sean Wain's actions were caused by the smoking cessation aid Chantix (varenicline), sold by Pfizer in the United States since 2006, and seeks compensatory and punitive damages. According to the filing, users of Chantix were not sufficiently warned at the time that it can cause rage, hostility, and suicide. Wain, according to the complaint, had been using Chantix for one to two weeks before he began experiencing side effects that led him to kill his wife and himself in May 2009. A number of side effects including mood swings and aggressive behavior have been linked to Chantix.

• On May 13, the Wall Street Journal reported that federal prosecutors are seeking about $1 billion to resolve a long-running probe into Johnson & Johnson's marketing of the antipsychotic drug Risperdal (risperidone). According to Securities and Exchange Commission filings, the government has for the past six years been conducting a probe into whether the company's Janssen Pharmaceutica unit promoted Risperdal for unapproved, off-label uses. A settlement of around $1 billion would be among the largest in a string of settlements related to off-label marketing of drugs in recent years. Prosecutors apparently used as a benchmark a 2009 settlement in which Eli Lilly paid $1.4 billion to resolve similar allegations regarding its antipsychotic Zyprexa (olanzapine).

Regulatory Briefs

• On April 6, the Food and Drug Administration (FDA) approved Invega (paliperidone) extended-release tablets for treatment of schizophrenia in adolescents aged 12 to 17. Invega was first approved in December 2006 for the treatment of schizophrenia in adults and is marketed in the United States by the Janssen Division of Ortho-McNeil-Janssen Pharmaceuticals.

  The efficacy of Invega in adolescents with schizophrenia was established in a six–week randomized, double-blind, placebo-controlled study using a fixed-dose weight-based treatment group design over a daily dose range of 1.5 mg to 12 mg. The study was conducted in several countries, including the United States, and involved adolescents aged 12 to 17 who met DSM-IV criteria for schizophrenia. Efficacy was evaluated using the Positive and Negative Syndrome Scale.

  Invega was adequately tolerated within the dose range of 3 mg to 12 mg a day. Adverse events were dose related. In the total paliperidone treatment group, the most commonly reported adverse events in this study were somnolence (13 percent), akathisia (9 percent), headache (9 percent), and insomnia (9 percent).

  Prescribing information for Invega is posted at <www.accessdata.fda.gov/drugsatfda_docs/label/2011/021999s020s024lbl.pdf>.

Clinical Trial Briefs

• On May 13, Takeda Pharmaceutical Company and H. Lundbeck A/S announced the initiation of a phase 3 clinical trial in Japan for Lu AA21004 in patients with major depressive disorder. This randomized, double-blind, and multicenter trial is expected to enroll about 360 patients and will evaluate the efficacy and safety of Lu AA21004 (5 mg and 10 mg) compared with placebo. The study is expected to be concluded within 18 months. The primary endpoint is change in Montgomery-Asberg Depression Rating Scale total score from baseline to eight weeks. Lu AA21004 is a structurally novel compound that is different from available antidepressants. Data from clinical trials conducted outside Japan have shown encouraging results for the potential efficacy and the tolerability profile of Lu AA21004. In addition to the Japanese study, the clinical trial program includes four ongoing short-term studies and two long-term safety studies.

• On May 11, Dainippon Sumitomo Pharma announced the results of a Pan-Asia study, a placebo-controlled trial of lurasidone (Latuda) to treat patients with schizophrenia.

  The study was a double-blind, placebo-controlled, six-week clinical trial conducted with schizophrenia patients in Japan, Korea, and Taiwan. Efficacy of lurasidone was evaluated using the Positive and Negative Syndrome Scale (PANSS) total score as the primary endpoint and the Clinical Global Impressions Severity Scale as the secondary endpoint.

  Lurasidone at 40 mg/day and 80 mg/day did not show a statistically significant improvement over placebo in PANSS total score change at the six-week study endpoint, despite a significant within-group reduction of the total PANSS score after treatment. This clinical trial is viewed as a failed study, as it was unsuccessful in establishing assay sensitivity. Despite the failure, company leaders believe they obtained useful data, which will assist with the design of future studies to support the registration of lurasidone in Japan.